Defining Dry Eye from a Clinical Perspective

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.     

Differential modes of nuclear localization signal (NLS) recognition by three distinct classes of NLS receptors

The targeting of karyophilic proteins to nuclear pores is mediated via the formation of a nuclear pore-targeting complex, through the interaction of nuclear localization signal (NLS) with its NLS receptor. Recently, a novel human protein, Qip1, was identified from a yeast two-hybrid system with DNA helicase Q1. This study demonstrates that Qip1 is a novel third class of NLS receptor that efficiently recognizes the NLS of the helicase Q1. Moreover, the data obtained in this study show that the specific interaction between Qip1 and the NLS of the helicase Q1 requires its upstream sequence of the minimal essential NLS. By using purified recombinant proteins alone in the digitonin-permeabilized cell-free transport system, it was demonstrated that the two known human NLS receptors, Rch1 and NPI-1, are able to transport all the tested NLS substrates into the nucleus, while Qip1 most efficiently transports the helicase Q1-NLS substrates, which contain its upstream sequence in so far as we have examined the system. Furthermore, in HeLa cell crude cytosol, it was found that endogenous Rch1 binds to all the tested NLS substrates, while the binding of endogenous NPI-1 is restricted to only some NLSs, despite the fact that NPI-1 itself shows binding activity to a variety of NLSs. These results indicate that at least three structurally and functionally distinct NLS receptors exist in the human single cell population, and suggest that the nuclear import of karyophilic proteins may be controlled in a complex manner at the NLS recognition step by the existence of a variety of NLS receptors with various specificities to each NLS.     

Sensorless control of synchronous reluctance motors using on‐line parameter identification method not affected by position estimation accuracy

This paper presents a novel on‐line parameter identification method for sensorless control of Synchronous Reluctance Motors (SynRMs). Although conventional sensorless control methods based on mathematical models usually need some complex measurements of motor parameters in advance, the proposed identification method does not require them and can be realized on‐line. The proposed method identifies motor parameters under sensorless control, so rotor position and velocity cannot be used to identify these parameters. However, the proposed method does not need rotor position and velocity, and identified parameters are not affected by these estimation errors. The sensorless control using identified motor parameters is realized, and the effectiveness of the proposed method is verified by experimental results. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 155(3): 62–69, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20258     

A load dispatch method using fractional programming and semidefinite programming

This paper describes a load dispatch method which minimizes power cost—[fuel cost]/[electric output]—for a power system with thermal plants and energy storage facilities. The proposed method employs fractional programming to convert a minimization problem with fractional objective function to a series of quadratic minimization problems, and semidefinite programming to solve converted problems. The method provides the optimum time‐dependent power output/input and storage level of energy storage facilities as well as time‐dependent power output of thermal plants. The method has been applied to a power system with five thermal plants, two energy storage facilities of various performances, and five load demands. The optimum load scheme of four time mesh points is obtained for the thermal plants and energy storage facilities. The fractional programming successfully converges the optimal scheme through a few iterations. The semidefinite programming deals with a variable matrix of 164 dimensions, and 185 inequality constraints. © 2001 Scripta Technica, Electr Eng Jpn, 138(2): 49–58, 2002     

Influence of third monomer on the crystal phase transition behavior of ethylene-tetrafluoroethylene copolymer

Crystal phase transition between the low- and high-temperature phases has been investigated for ethylene (E)-tetrafluoroethylene (TFE) alternating copolymer (ETFE) containing the third monomeric species by the temperature dependent measurements of wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) and differential scanning calorimetry. Nonafluoro-1-hexene (NFH) and hexafluoropropylene (HFP) were chosen as the third monomers, where they are different in the side-branch length, -(CF₂)₃CF₃ and -CF₃, respectively. In the case of E/TFE/NFH copolymer (ET-C4F9), the crystal phase transition temperature of the original ETFE two-components copolymer was not very much affected by the existence of NFH in the range of NFH content from 0.7 to 3 mol%. Contrarily, the crystal phase transition temperature of E/TFE/HFP copolymer (ET-CF3) was found to decrease drastically with increasing HFP content. The melting temperature and the higher-order structure were also affected sensitively depending on the HFP content. This difference in phase transition behavior between ET-C4F9 and ET-CF3 copolymers is reasonably interpreted as follows: the short side groups (-CF₃) of HFP monomeric unit are included in the crystal lattice of E/TFE chains and the unit cell is expanded gradually with an increment of the HFP content, resulting in the decrease in phase transition point because of easier thermal motion of the chains. On the other hand, the long side groups [-(CF₂)₃CF₃] of NFH monomeric units are excluded out of the crystal lattice and located on the lamellar surfaces or in the amorphous region and do not affect very much the phase transition temperature even when the NFH content is increased. In association with such a change in crystal structure, the long period of stacked lamellar structure was found to decrease remarkably in the case of NFH, whereas it does not change very much for HFP, consistent with the interpretation of the above-mentioned WAXD data.     

Atomic force microscopic study on DNA-wrapping for different diameter single-wall carbon nanotubes

DNA-wrapped single-wall carbon nanotubes (DNA-SWNT hybrids) prepared from different diameter HiPco- and Arc-SWNTs were investigated by atomic force microscopy. The mean diameter of DNA-HiPco-SWNT hybrids is 1.94 nm that is consistent with one HiPco-SWNT (~ 0.9 nm) wrapped by DNA (~ 1 nm). On the other hand, the mean diameter of DNA-Arc-SWNT hybrids is 3.74 nm that can correspond to one Arc-SWNT (~ 1.4 nm) wrapped by several layers of DNA. It is suggested that the DNA-wrapping mechanism for large diameter Arc-SWNTs is different from that for small diameter HiPco-SWNTs.     

The rotational angle in osteoarthritic knees

The desire to work is deeply rooted in the human psyche and involves both intrinsic and extrinsic factors. If this is indeed the case, then this form of human activity should be considered to be an important element of our lives and therefore worthy of intervention when circumstances restrict an individual's engagement with it. To investigate the therapeutic nature of work for people with enduring mental health problems, the author conducted a pilot case study of a work rehabilitation scheme in the United Kingdom. The main theme to emerge from the study was that of purposeful activity.     

An Engineered Biliverdin-Compatible Cyanobacteriochrome Enables a Unique Ultrafast Reversible Photoswitching Pathway

Cyanobacteriochromes (CBCRs) are promising optogenetic tools for their diverse absorption properties with a single compact cofactor-binding domain. We previously uncovered the ultrafast reversible photoswitching dynamics of a red/green photoreceptor AnPixJg2, which binds phycocyanobilin (PCB) that is unavailable in mammalian cells. Biliverdin (BV) is a mammalian cofactor with a similar structure to PCB but exhibits redder absorption. To improve the AnPixJg2 feasibility in mammalian applications, AnPixJg2_BV4 with only four mutations has been engineered to incorporate BV. Herein, we implemented femtosecond transient absorption (fs-TA) and ground state femtosecond stimulated Raman spectroscopy (GS-FSRS) to uncover transient electronic dynamics on molecular time scales and key structural motions responsible for the photoconversion of AnPixJg2_BV4 with PCB (Bpcb) and BV (Bbv) cofactors in comparison with the parent AnPixJg2 (Apcb). Bpcb adopts the same photoconversion scheme as Apcb, while BV4 mutations create a less bulky environment around the cofactor D ring that promotes a faster twist. The engineered Bbv employs a reversible clockwise/counterclockwise photoswitching that requires a two-step twist on ~5 and 35 picosecond (ps) time scales. The primary forward P_fr → P_o transition displays equal amplitude weights between the two processes before reaching a conical intersection. In contrast, the primary reverse P_o → P_fr transition shows a 2:1 weight ratio of the ~35 ps over 5 ps component, implying notable changes to the D-ring-twisting pathway. Moreover, we performed pre-resonance GS-FSRS and quantum calculations to identify the Bbv vibrational marker bands at ~659,797, and 1225 cm⁻¹. These modes reveal a stronger H-bonding network around the BV cofactor A ring with BV4 mutations, corroborating the D-ring-dominant reversible photoswitching pathway in the excited state. Implementation of BV4 mutations in other PCB-binding GAF domains like AnPixJg4, AM1_1870g3, and NpF2164g5 could promote similar efficient reversible photoswitching for more directional bioimaging and optogenetic applications, and inspire other bioengineering advances.     

Adsorption of trypsin onto poly(2-hydroxyethyl methacrylate)/polystyrene composite microspheres and its enzymatic activity

Poly(2-hydroxyethyl methacrylate)/polystyrene (PHEMA/PS) composite microspheres were produced by emulsifier-free seeded emulsion polymerization for styrene in the presence of PHEMA seed particles. Effects of the surface characteristics of the PHEMA/PS composite microspheres on the adsorption immobilization of trypsin and on its enzymatic activity were discussed. Above 5 mol% of HEMA content, trypsin molecules adsorbed had high activity, 65–100% of the activity of free trypsin. The excellence of the composite microspheres as a carrier for trypsin seems to be closely related with the surface heterogeneity consisting of both hydrophilic and hydrophobic parts.